An intensive effort was directed at studying the epidemiologic, etiologic, immunologic, and clinical aspects of the acquired immunodeficiency syndrome (AIDS). Over 150 patients with this illness have been enrolled in programs at the NIH. The LIR has performed the immunologic monitoring on all these patients. These large-scale studies established the fact that those patients with Kaposi's sarcoma alone are at the healthiest end of the immunologic spectrum. The AIDS patients were characterized as having marked quantitative and qualitative defects in cell mediated immunity. A selective defect in the ability of the helper T cell to respond to soluble antigen was delineated which provided an early clue to the T cell tropic nature of the subsequently uncovered etiologic agent. Examination of the B cells of these patients revealed a marked degree of polyclonal activation with a refractoriness to the normal signals for in vitro B cell activation coupled with an enhanced responsiveness to B cell growth factors. A series of clinical studies were carried out attempting in vivo to correct the immunodeficiency of these patients. Trials of both natural product gamma interferon and interleukin-2 were completed. While unable to effect an alteration in the clinical course of the patients, these trials revealed much concerning the pharmacokinetics of these new agents and their ability to modulate the human immune system. Peripheral lymphocyte transfers were carried out in 2 sets of identical twins, in each case one with AIDS and one healthy. In both instances only partial immune reconstitution was noted to occur, suggesting persistence of the AIDS agent. Finally, a variety of studies were initiated comparing various diagnostic techniques and therapies for several of the infectious complications of AIDS, particularly Pneumocystis carinii pneumonia and disseminated Mycobacterium avium-intracellulare.